TOP-promoter elements control the relative ratio of intron-encoded snoRNA versus spliced mRNA biosynthesis

In vertebrates almost all snoRNAs are encoded in introns of a specific subclass of polII transcripts: the TOP genes. The majority of these RNAs originate through debranching of the spliced introns, the rest through endonucleolytic cleavage of the precursor that contains them. In both cases it has been suggested that snoRNP factors associate at early steps during transcription and control snoRNA biogenesis. Here, we analyzed the specific case of the U16 snoRNA that was shown to originate mainly through endonucleolytic cleavage. We show that TOP promoter elements determine a specific ratio of snoRNA and mRNA production. Under the control of these sequences the snoRNA is likely to originate from both splicing and cleavage of the pre-mRNA. Conversely, canonical polII promoter elements seem not to be compatible with snoRNA release through the cleavage reaction and produce a lower snoRNA/mRNA ratio. In addition, we show that the proximal part of the TOP promoter is responsible for this peculiar post-transcriptional process that controls the relative ratio between snoRNA and mRNA.